The purpose of this investigation is to develop test methodology for evaluation of the biologic properties of endodontic materials with the long-range goal of suggesting biologic standards and specifications in accordance with the Medical Device Bill passed by the Congress 28 May 1976. Presently, the only tests which come near to expressing the true tissue reactions to the materials under usage conditions are the expensive and cumbersome experimentations in primates or the "trial and error" in human patients - which should be avoided because it in fact involves human experimentation. It is proposed to investigate whether or not a correlation exists between specific primary screening tests and usage tests with the future aim of replacing the expensive usage tests with adequate, reliable, and relevant screening methods which will reduce the cost of testing while securing biologically safe materials to the patient. The proposed experimental systems and techniques for the correlation study are the following: (1) HeLa cells and human fibroblasts in tissue culture utilizing 51Cr release to measure cytotoxicity. (2) Assessment of enhanced vascular permeability and cellular response in connective tissue in rats after intradermal injection of the material. (3) Evaluation of response to implants in soft tissues and bone tissues in guinea pigs. (4) Evaluation of inflammatory response in remaining pulp tissue and in periapical tissue of monkeys. The methods of evaluation include radio-isotope measurement, SEM, and electron probe, and histopathological techniques. The correlation of these tests will provide economical and relevant screening methods which may be used by manufacturers during their development of new products and for their quality control. Ultimately, it secures biologically safe materials to the patient population, and eliminates inefficient and/or toxic materials from use.